Acute inflammation

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Acute inflammation

  1. 1. • Egyptian papyrus - 3000 B.C.• Celsus (Roman in 1st century A.D.)Rubor - Tumor - Calor - Dolorredness - swelling - heat - pain• Virchow added functio laesa laterHistory
  2. 2. What is inflammation?What is inflammation? Inflammation –Inflammation –Protective response intended to eliminate the initialProtective response intended to eliminate the initialcause of cell injury and the necrotic cells and tissuescause of cell injury and the necrotic cells and tissuesarising from the injuryarising from the injury Inflammation is intimately associated with theInflammation is intimately associated with therepair process which includes parenchymal cellrepair process which includes parenchymal cellregeneration and scarringregeneration and scarring
  3. 3.  Acute - minutes to daysAcute - minutes to days Characterized by fluid and proteinCharacterized by fluid and protein PMN’sPMN’s Exudate SG > 1.020Exudate SG > 1.020 Chronic - weeks to yearsChronic - weeks to years Lymphocytes and macrophagesLymphocytes and macrophages ACUTE Inf - PMN’s (ACUTE Inf - PMN’s (PolyPolymorphonuclear Cells)morphonuclear Cells) CHRONIC Inf -CHRONIC Inf - MonoMononuclear Cellsnuclear CellsInflammationInflammationEXUDATE
  4. 4. Acute inflammation“The immediate and early response to aninjurious agent”Chronic inflammation“Inflammation of prolonged duration (weeksor months) in which active inflammation,tissue destruction, and attempts at repair areproceeding simultaneously“
  5. 5. Exudate• ↑ vascular permeability• high protein & cell debris• SG > 1.020Transudate• normal vascular permeability• hydrostatic pres. → plasma ultrafiltrate• low protein (mostly albumin)• SG < 1.012Edema• exudate or transudate ; interstitium orcavity
  6. 6. Acute inflammationAcute inflammationmajor componentsmajor components Transient vasoconstrictionTransient vasoconstriction VasodilatationVasodilatation Endothelial permeabilityEndothelial permeability Extravasation of PMNsExtravasation of PMNs
  7. 7. Five classic local signs of acuteFive classic local signs of acuteinflammationinflammation HeatHeat RednessRedness SwellingSwelling PainPain Loss of functionLoss of function Calor – vasodilatationCalor – vasodilatation Rubor – vasodilatationRubor – vasodilatation Tumor – vascular permeabilityTumor – vascular permeability Dolor – mediator release/PMNsDolor – mediator release/PMNs Functio laesa – loss of functionFunctio laesa – loss of function
  8. 8. Vascular changesVascular changesyou need to know thisyou need to know this Transient vasoconstrictionTransient vasoconstriction VasodilationVasodilation Exudation of protein rich fluidExudation of protein rich fluid Blood stasisBlood stasis MarginationMargination Emigration/TransmigrationEmigration/Transmigration
  9. 9. Vascular changesProtein exits vessels :↓ intravascular osmoticpressure↑ intravascular hydrostaticpressureEndothelial gaps at intercellularjunctions:* immediate transient response* histamine, bradykinin,leukotrienes, substance P
  10. 10. Vascular permeabilityVascular permeability Vasodilation – increased blood flowVasodilation – increased blood flow Increased intravascular hydrostatic pressureIncreased intravascular hydrostatic pressure TransudateTransudate - ultrafiltrate blood plasma (contains little- ultrafiltrate blood plasma (contains littleprotein)protein) Again, this is very transient and just gets the process started.Again, this is very transient and just gets the process started.Think acute inflammation, think EXUDATEThink acute inflammation, think EXUDATE ExudateExudate - (protein-rich with PMNs)- (protein-rich with PMNs) Exudate is the characteristic fluid of acute inflammationExudate is the characteristic fluid of acute inflammation Intravascular osmotic pressure decreasesIntravascular osmotic pressure decreases Osmotic pressure of interstitial fluid increasesOsmotic pressure of interstitial fluid increases Outflow of water and ions -Outflow of water and ions - edemaedema
  11. 11. How do endothelial cellsHow do endothelial cellsbecome permeable?become permeable? Endothelial cell contractionEndothelial cell contraction Junctional retractionJunctional retraction Direct endothelial injury (immediate sustainedDirect endothelial injury (immediate sustainedresponse)response) Leukocyte-dependent endothelial injuryLeukocyte-dependent endothelial injury Increased transcytosis of fluidIncreased transcytosis of fluid
  12. 12. Direct endothelial injuryDirect endothelial injury(immediate sustained response)(immediate sustained response) Endothelial cell necrosis and detachmentEndothelial cell necrosis and detachment Result of severe injury or burnResult of severe injury or burn Occurs immediately and lasts until vesselOccurs immediately and lasts until vesselrepairedrepaired
  13. 13.  Occurs at sites of leukocyte accumulationOccurs at sites of leukocyte accumulation Due to leukocyte activation which releasesDue to leukocyte activation which releasesproteolytic enzymes and toxic oxygenproteolytic enzymes and toxic oxygenLeukocyte-dependent endothelialLeukocyte-dependent endothelialinjuryinjury
  14. 14. Leukocyte Cellular EventsLeukocyte Cellular Events Margination and RollingMargination and Rolling Adhesion and TransmigrationAdhesion and Transmigration Migration into interstitial tissueMigration into interstitial tissue
  15. 15. SLOWING CONCENTRATIONMargination Rolling AdhesionTransmigration
  16. 16. Selectins CAMSIntegrinsMucin-like glycoproteins(Sialyl-Lewis X PSL-1 & ESL-1)Weak and transientbindingResults in rollingIntegrins upregulated and activatedfor increased affinity to CAMSResults in firm adhesion
  17. 17. MarginationMargination Normal flow - RBCs and WBCs flow in theNormal flow - RBCs and WBCs flow in thecenter of the vesselcenter of the vessel AA cell poorcell poor plasma is flowing adjacent toplasma is flowing adjacent toendotheliumendothelium As blood flow slows, WBCs collect along theAs blood flow slows, WBCs collect along theendotheliumendothelium  MarginationMargination
  18. 18. Endothelial ActivationEndothelial Activation The underlying stimulus causes release ofThe underlying stimulus causes release ofmediators which activate the endotheliummediators which activate the endotheliumcausing selectins and other mediators to becausing selectins and other mediators to bemoved quickly to the surfacemoved quickly to the surface
  19. 19. SelectinsSelectins Selectins bind selected sugarsSelectins bind selected sugars SeSelected +lected + LectinsLectins (sugars) = Selectins(sugars) = Selectins Some selectins are present on endothelial cells (E-Selectin)Some selectins are present on endothelial cells (E-Selectin) Some selectins are present on leukocytes (L-Selectin)Some selectins are present on leukocytes (L-Selectin) Some selectins are present on platelets (P-Selectin)Some selectins are present on platelets (P-Selectin) Weak & transient bindingWeak & transient binding Results inResults in rollingrolling
  20. 20. Fig 3-9Fig 3-9
  21. 21. RollingRolling Selectins transiently bind to receptorsSelectins transiently bind to receptors PMNs bounce or roll alongPMNs bounce or roll along  RollingRolling
  22. 22. AdhesionAdhesion Mediated by integrins ICAM-1 and VCAM-1Mediated by integrins ICAM-1 and VCAM-1
  23. 23. TransmigrationTransmigration Mediated/assisted by PECAM-1 & ICAM-1 (Integrins)Mediated/assisted by PECAM-1 & ICAM-1 (Integrins) Diapedesis (cells crawling)Diapedesis (cells crawling) Primary in venulesPrimary in venules Collagenases degrade BMCollagenases degrade BM ↑↑ PermeabilityPermeability
  24. 24. ChemotaxisChemotaxis Movement toward the site of injury along aMovement toward the site of injury along achemical gradientchemical gradient Chemotactic factors includeChemotactic factors include Complement components (20 serum proteins)Complement components (20 serum proteins) Arachadonic acid (AA) metabolitesArachadonic acid (AA) metabolites Soluble bacterial productsSoluble bacterial products Chemokines, cytokinesChemokines, cytokines
  25. 25. Phagocytosis & DegranulationPhagocytosis & Degranulation Phagocytosis (engulf and destroy)Phagocytosis (engulf and destroy) Degranulation and the oxidative burst destroyDegranulation and the oxidative burst destroythe engulfed particlethe engulfed particle Recognition & attachmentRecognition & attachment Opsonins coat target and bind to leukocytesOpsonins coat target and bind to leukocytes EngulfmentEngulfment Killing/degradationKilling/degradation OO22 dep: Reactive Odep: Reactive O22 species in lysosomes & ECspecies in lysosomes & EC OO22 indep: Bactericidal permeability agents,indep: Bactericidal permeability agents,lysozyme, MBP, lactoferrinlysozyme, MBP, lactoferrin
  26. 26. Leukocyte-induced tissueLeukocyte-induced tissueinjuryinjury Lysosomal enzymes are released into theLysosomal enzymes are released into theextracellular space during phagocytosis causingextracellular space during phagocytosis causingcell injury and matrix degradationcell injury and matrix degradation Activated leukocytes release reactive oxygenActivated leukocytes release reactive oxygenspecies and products of arachidonic acidspecies and products of arachidonic acidmetabolism which can injure tissue andmetabolism which can injure tissue andendothelial cellsendothelial cells These events underlie many human diseases (e.g.These events underlie many human diseases (e.g.Rheumatoid arthritis)Rheumatoid arthritis)
  27. 27. Table 3-3Table 3-3GeneticGenetic DefectDefectLAD 1LAD 1 B chain of CD11/CD18 integrinsB chain of CD11/CD18 integrinsLAD 2LAD 2 Sialylated oligosaccharideSialylated oligosaccharideNeutrophil-specific granuleNeutrophil-specific granuledeficiencydeficiencyAbsence of neutrophil-specificAbsence of neutrophil-specificgranulesgranulesCGDCGDX-linkedX-linkedARARDefective chemotaxisDefective chemotaxisNADPH oxidatise (membrane)NADPH oxidatise (membrane)NADPH oxidase (cytoplasm)NADPH oxidase (cytoplasm)MPO deficiencyMPO deficiency Absent MPO-H2O2 systemAbsent MPO-H2O2 systemChediak-Higashi syndromeChediak-Higashi syndrome Lysosomal defectLysosomal defectAcquiredAcquiredThermal injury, DM, CA, sepsisThermal injury, DM, CA, sepsis ChemotaxisChemotaxisDialysis, DMDialysis, DM AdhesionAdhesionLeukemia, anemia, sepsis, DM,Leukemia, anemia, sepsis, DM,neonates, malnutritionneonates, malnutritionPhagocytosis & microbicidalPhagocytosis & microbicidalactivityactivity
  28. 28. Leukocyte adhesion deficiency 1Leukocyte adhesion deficiency 1(LAD-1)(LAD-1) Recurrent bacterial infectionsRecurrent bacterial infections Inflammatory lesions lack neutrophil infiltrateInflammatory lesions lack neutrophil infiltrate High numbers of neutrophils in the circulationHigh numbers of neutrophils in the circulation Neutrophils from patients can roll but do not stickNeutrophils from patients can roll but do not stick ΒΒ chain of CD11/CD18 integrinchain of CD11/CD18 integrin Transfuse patients with normal neutrophils and theyTransfuse patients with normal neutrophils and theycan emigratecan emigrate
  29. 29. Mechanism of leukocyteMechanism of leukocyteadhesion deficiency 1 (LAD -1)adhesion deficiency 1 (LAD -1) Absence of integrins on neutrophilsAbsence of integrins on neutrophils Mutation in n-terminal region of the integrinMutation in n-terminal region of the integrin ββ chainchaininhibits proper integrin assemblyinhibits proper integrin assembly Normal function is restored following transfection ofNormal function is restored following transfection ofpatient cells with cDNA forpatient cells with cDNA for ββ chainchain
  30. 30. Chediak-Higashi SyndromeChediak-Higashi Syndrome This syndrome has been on every board test sinceThis syndrome has been on every board test sinceNoahNoah Defect in chemotaxis and lysosomal degranulationDefect in chemotaxis and lysosomal degranulationinto phagosomesinto phagosomes
  31. 31. Chronic Granulomatous DiseaseChronic Granulomatous Disease Defect in NADPH oxidase systemDefect in NADPH oxidase system Marked decrease in ability to kill microorganismsMarked decrease in ability to kill microorganisms
  32. 32. Chemical mediators of inflammationChemical mediators of inflammation Plasma-derivedPlasma-derived Circulating precursorsCirculating precursors Have to be activatedHave to be activated Cell-derivedCell-derived Sequestered intracellularSequestered intracellular Synthesized de novoSynthesized de novo Most mediators bind to receptors on cell surface butMost mediators bind to receptors on cell surface butsome have direct enzymatic or toxic activitysome have direct enzymatic or toxic activity Mediators are tightly regulatedMediators are tightly regulated
  33. 33. Chemotacticfactors (eg. c5a)Chemotacticfactors (eg. c5a)TissueinjuryTissueinjuryVasoactivemediators(eg. histamine)Vasoactivemediators(eg. histamine)Increased vascularpermeabilityIncreased vascularpermeabilityRecruitment of inflammatorycellsRecruitment of inflammatorycellsEdemaEdema PMNsPMNs MonosMonosProduction ofinflammatorymediatorsProduction ofinflammatorymediatorsAcuteinflammationAcuteinflammationChronicinflammationChronicinflammation
  34. 34. Plasma Mediator Systems - Interaction 1.   Kinin2.   Clotting3.   Complement4.   Fibrinolytic 
  35. 35. C5C5aPlasminogen  →  PlasminC3C3a   Fibrin   →  FSPsProthrombin → ThrombinFibrinogen XIIKininComplementClottingFibrinolyticFibrinopeptidesPrekallikreinXIIa  Kallikrein High Mol. Wt. Kininogen BradykininPlasma Mediator Systems - Interaction
  36. 36. Kinin cascadeKinin cascade Leads to formation of bradykininLeads to formation of bradykinin Bradykinin causesBradykinin causes Increased vascular permeabilityIncreased vascular permeability Arteriolar dilatationArteriolar dilatation Smooth muscle contractionSmooth muscle contraction Bradykinin is short lived (kininases)Bradykinin is short lived (kininases) Vascular actions similar to histamineVascular actions similar to histamine
  37. 37. Complement systemComplement system Role in immunity (C5-9 complex)Role in immunity (C5-9 complex) Membrane Attack Complex (MAC C5-9)Membrane Attack Complex (MAC C5-9) Punches a hole in the membranePunches a hole in the membrane
  38. 38. Complement systemComplement system Role in inflammation (c3a and c5a)Role in inflammation (c3a and c5a) Vascular effectsVascular effects Increase vascular permeability and vasodilationIncrease vascular permeability and vasodilation Similar to histamineSimilar to histamine Activates lipoxygenase pathway of arachidonic acidActivates lipoxygenase pathway of arachidonic acidmetabolism (c5a)metabolism (c5a)
  39. 39. Complement systemComplement system Leukocyte activation, adhesion and chemotaxis (c5a)Leukocyte activation, adhesion and chemotaxis (c5a) PhagocytosisPhagocytosis c3b acts as opsonin and promotes phagocytosis by cellsc3b acts as opsonin and promotes phagocytosis by cellsbearing receptors for c3bbearing receptors for c3b
  40. 40. Inflammatory Mediators fromInflammatory Mediators fromComplementComplementAnaphylatoxinsAnaphylatoxins::C3a, C5a, & C4aC3a, C5a, & C4a trigger mast cells to release histaminetrigger mast cells to release histamineand cause vasodilatationand cause vasodilatationC5aC5a also activates the lipoxygenase system in PMNsalso activates the lipoxygenase system in PMNsand monocytesand monocytes →→ release of inflammatoryrelease of inflammatorymediatorsmediatorsLeukocyte activation, adhesion, & chemotaxisLeukocyte activation, adhesion, & chemotaxis::C5aC5a activates leukocytes, promotes leukocyte bindingactivates leukocytes, promotes leukocyte bindingto endothelium via integrins and is chemotactic forto endothelium via integrins and is chemotactic forPMNs, monos, eos, & basosPMNs, monos, eos, & basos
  41. 41. Inflammatory Mediators fromInflammatory Mediators fromComplementComplementPhagocytosisPhagocytosis::C3b and C3biC3b and C3bi are opsoninsare opsoninsControlControl::Convertases are destabilized by "decay acceleratingConvertases are destabilized by "decay acceleratingfactor" (DAF)factor" (DAF)Inability to express DAF causesInability to express DAF causes paroxysmal nocturnalparoxysmal nocturnalhemoglobinuriahemoglobinuriaC1 inhibitor (C1INH) deficiency causesC1 inhibitor (C1INH) deficiency causes hereditaryhereditaryangioneurotic edemaangioneurotic edema
  42. 42. Vasoactive aminesVasoactive amines HistamineHistamine Found in mast cells, basophils and plateletsFound in mast cells, basophils and platelets Released in response to stimuliReleased in response to stimuli Promotes arteriolar dilation and venularPromotes arteriolar dilation and venularendothelial contractionendothelial contraction results in widening of interendothelial cell junctionsresults in widening of interendothelial cell junctionswith increased vascular permeabilitywith increased vascular permeability SerotoninSerotonin Vasoactive effects similar to histamineVasoactive effects similar to histamine Found in plateletsFound in platelets Released when platelets aggregateReleased when platelets aggregate
  43. 43. Bradykinin: Potent biomolecule 1. Vasodilatation2. Increased vascular permeability3. Contraction of smooth muscle4. Pain on injection5. Short life, kininase degrades Bradykinin: Potent biomolecule 1. Vasodilatation2. Increased vascular permeability3. Contraction of smooth muscle4. Pain on injection5. Short life, kininase degrades Factor XII activated by:1. Plasmin2. Kallikrein3. Collagen & basement membrane4. Activated platelets5. Co-factor = HMWKFactor XII activated by:1. Plasmin2. Kallikrein3. Collagen & basement membrane4. Activated platelets5. Co-factor = HMWK↑ Vascular Permeability:- Bradykinin- Fibrionopeptides- Fibrin Split Prod.- Factor Xa- Leukotrienes↑ Vascular Permeability:- Bradykinin- Fibrionopeptides- Fibrin Split Prod.- Factor Xa- Leukotrienes
  44. 44. Arachidonic Acid (AA)Arachidonic Acid (AA) Where is it located?Where is it located? AA is a component of cell membrane phospholipidsAA is a component of cell membrane phospholipids The breakdown of AA into its metabolitesThe breakdown of AA into its metabolitesproduces a variety of biologic effectsproduces a variety of biologic effects
  45. 45. Arachidonic acid metabolitesArachidonic acid metabolites Metabolites of AA - short-range hormonesMetabolites of AA - short-range hormones AA metabolites act locally at site of generationAA metabolites act locally at site of generation Rapidly decay or are destroyedRapidly decay or are destroyed
  46. 46. Arachidonic AcidArachidonic Acid AA is released from the cell membrane byAA is released from the cell membrane byphospholipasesphospholipases which have themselves beenwhich have themselves beenactivated by various stimuli and/oractivated by various stimuli and/orinflammatory mediatorsinflammatory mediators AA metabolism occurs via two major pathwaysAA metabolism occurs via two major pathwaysnamed for the enzymes that initiate thenamed for the enzymes that initiate thereactions;reactions; lipoxygenaselipoxygenase andand cyclooxygenasecyclooxygenase
  47. 47. AA metabolites (eicosanoids)Cyclooxygenases synthesizeProstaglandinsThromboxanesLipoxygenases synthesizeLeukotrienesLipoxins
  48. 48. PGG2↓PGH2PGI2ProstacyclinTXA2ThromboxanePGD2 ; PGE2PGF2VasodilatationInhibits Platelet AggregationVasoconstrictionPromotes Platelet AggregationVasodilatationEdemaPGI2TXA2
  49. 49. Arachidonic Acid PathwaysArachidonic Acid Pathwaysyou need to know thisyou need to know this LipoxygenaseLipoxygenase 5-HETE5-HETE ChemotaxisChemotaxis 5-HPETE5-HPETE Leukotriene generationLeukotriene generation LeukotrienesLeukotrienes VasoconstricitonVasoconstriciton BronchospasmBronchospasm Increased vascularIncreased vascularpermeabilitypermeability LipoxygenaseLipoxygenase 5-HETE5-HETE ChemotaxisChemotaxis 5-HPETE5-HPETE Leukotriene generationLeukotriene generation LeukotrienesLeukotrienes VasoconstricitonVasoconstriciton BronchospasmBronchospasm Increased vascularIncreased vascularpermeabilitypermeability CyclooxygenaseCyclooxygenase ProstaglandinsProstaglandins VasodilatationVasodilatation Increased vascularIncreased vascularpermeabilitypermeability ProstacyclinProstacyclin VasodilatationVasodilatation Inhibits platlelet aggregationInhibits platlelet aggregation Thromboxane A2Thromboxane A2 VasoconstrictionVasoconstriction Promotes platlelet aggregationPromotes platlelet aggregation CyclooxygenaseCyclooxygenase ProstaglandinsProstaglandins VasodilatationVasodilatation Increased vascularIncreased vascularpermeabilitypermeability ProstacyclinProstacyclin VasodilatationVasodilatation Inhibits platlelet aggregationInhibits platlelet aggregation Thromboxane A2Thromboxane A2 VasoconstrictionVasoconstriction Promotes platlelet aggregationPromotes platlelet aggregation
  50. 50. Arachidonic Acid PathwaysArachidonic Acid Pathwaysyou need to know thisyou need to know this LipoxygenaseLipoxygenase 5-HETE, 5-HPETE,5-HETE, 5-HPETE,LeukotrienesLeukotrienes Spasm (Vaso, Broncho)Spasm (Vaso, Broncho) LipoxygenaseLipoxygenase 5-HETE, 5-HPETE,5-HETE, 5-HPETE,LeukotrienesLeukotrienes Spasm (Vaso, Broncho)Spasm (Vaso, Broncho) CyclooxygenaseCyclooxygenase Prostaglandins - EDEMAProstaglandins - EDEMA Prostacyclin vs TXA2Prostacyclin vs TXA2 Vasodilatation vs.Vasodilatation vs.VasoconstrictionVasoconstriction Platelet aggregationPlatelet aggregationInhibits vs. promotesInhibits vs. promotes CyclooxygenaseCyclooxygenase Prostaglandins - EDEMAProstaglandins - EDEMA Prostacyclin vs TXA2Prostacyclin vs TXA2 Vasodilatation vs.Vasodilatation vs.VasoconstrictionVasoconstriction Platelet aggregationPlatelet aggregationInhibits vs. promotesInhibits vs. promotes
  51. 51. Arachidonic Acid MetabolitesArachidonic Acid Metabolites Participate in every aspect of acute inflammationParticipate in every aspect of acute inflammation Effective Anti-inflammatory agents act on AA pathwaysEffective Anti-inflammatory agents act on AA pathways Aspirin and Non-Steroidal Anti-inflammatory DrugsAspirin and Non-Steroidal Anti-inflammatory Drugs(NSAID’s) - Cyclooxygenase path(NSAID’s) - Cyclooxygenase path Steroids act, in part, by inhibiting Phospholipase A2Steroids act, in part, by inhibiting Phospholipase A2
  52. 52. Platelet-Activating FactorPlatelet-Activating Factor(PAF)(PAF) Another phospholipid-derived mediator released byAnother phospholipid-derived mediator released byphospholipasesphospholipases Induces aggregation of plateletsInduces aggregation of platelets Causes vasoconstriction and bronchoconstrictionCauses vasoconstriction and bronchoconstriction 100 to 1,000 times more potent than histamine in100 to 1,000 times more potent than histamine ininducing vasodilation and vascular permeabilityinducing vasodilation and vascular permeability Enhances leukocyte adhesion, chemotaxis,Enhances leukocyte adhesion, chemotaxis,degranulation and the oxidative burstdegranulation and the oxidative burst It does everything!It does everything!
  53. 53. CytokinesCytokines Polypeptides that are secreted by cellsPolypeptides that are secreted by cells Act to regulate cell behaviorsAct to regulate cell behaviors Autocrine, paracrine or endocrine effectsAutocrine, paracrine or endocrine effects These “biological response modifiers” are beingThese “biological response modifiers” are beingactively investigated for therapeutic use inactively investigated for therapeutic use incontrolling the inflammatory response.controlling the inflammatory response.
  54. 54. 1. Macrophages make IL-1 & TNF-α2. T-cells make TNF-β (lymphotoxin)3. Can be autocrine, paracrine, endocrine4. IL-1, TNF, IL-6  acute phase responses,fever, (appetite, slow wave sleep, ↑ circ.pmn,↑ ACTH, ↑ corticosteroids)5. TNF notable for role in septic shock andmaintenance of body mass (cachexia in cancerfrom ↑ ↑ TNF-α )Lymphocyte function
  55. 55. Selected Inflammatory Cells &Selected Inflammatory Cells &Their ChemokinesTheir ChemokinesTarget CellTarget Cell Important ChemokinesImportant ChemokinesNeutrophilsNeutrophils IL-8, GroIL-8, Groαα,, ββ,, γγ, others, othersMonocytesMonocytes MIP-1MIP-1αα, MIP-1, MIP-1ββ, MCP-1,2,3, MCP-1,2,3EosinophilsEosinophils EotaxinEotaxinLymphocytesLymphocytes LymphotaxinLymphotaxinBasophilsBasophils IL-8, MIP-1IL-8, MIP-1αα, MCP-1,3, RANTES, MCP-1,3, RANTES
  56. 56. Nitric OxideNitric Oxide NO is a soluble free radical gasNO is a soluble free radical gas Made by nitric oxide synthetase (NOS) inMade by nitric oxide synthetase (NOS) inendothelium (eNOS), macrophages (iNOS),endothelium (eNOS), macrophages (iNOS),and specific neurons in the brain (nNOS)and specific neurons in the brain (nNOS) Broad range of functions and effects that areBroad range of functions and effects that areshort rangeshort range Vasodilatation by relaxing smooth muscle.Vasodilatation by relaxing smooth muscle. ↓↓ platelet aggregationplatelet aggregation Inhibits mast cellsInhibits mast cells Regulates leukocyte recruitmentRegulates leukocyte recruitment
  57. 57. Outcomes of Acute InflammationOutcomes of Acute Inflammation ResolutionResolution FibrosisFibrosis Abscess formationAbscess formation Progression to chronic inflammationProgression to chronic inflammation

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