This document summarizes the roles of chemical mediators in acute inflammation in 3 phases: vascular changes, chemotaxis, and other effects. It describes how histamine, bradykinin, C3a, C5a, prostaglandins, leukotriene B4, leukotrienes C4 and D4, platelet-activating factor, IL-1, TNF, and chemokines mediate increased vascular permeability, chemotaxis of leukocytes, pain, fever, and tissue damage during acute inflammation. It also outlines the pathways of leukotriene and prostaglandin synthesis from arachidonic acid and their functions in inflammation.

1. Mediator Kimiawi
Pada Radang
• Mahmud Ghaznawie
• Dept Pathology

3. Aktifasi Leukosit
Leukosit memiliki reseptor untuk stimuli tertentu

4. 1. Walaupun faktor pencetusnya
berbeda, reaksi radangnya sama
2. Reaksi radang tidak berhubungan
dengan persarafan jaringan
“Chemical substances mediate all
phases of acute inflammation”
Thomas, Lewis (1913-1993)

5. Mediator kimiawi pada peradangan

6. Vasodilatation
• Histamine
• Prostaglandins
• Nitric oxide
Increase of permeability
• Histamine
• Anaphylatoxins C3a and C5a
• Kinins
• Leukotrienes C, D, and E
• PAF
• Substance P
Chemotaxis
• Complement fragment C5a
• Lipoxygenase products,
lipoxins & leukotrines (LTB4)
• Chemokines
Tissue Damage
• Lysosomal products
• Oxygen-derived radicals
• Nitric Oxyde

7. Prostaglandins
• Vasodilatasi
• Nyeri
• Demam
• Edema lokal
IL-1 and TNF
• Interaksi endotel-leukosit
• Rekrutmen leukosit

8. VASODILATASI

9. Basofil & Sel Mast
Histamin

10. Mast Cells & Allergy

11. Konten granula sel neutrofil
(leukosit pmn)

12. LEUKOTRIEN & PROSTAGLANDIN

13. Leukotrien dan Prostaglandin:
Mediator pro inflamasi yang kuat
Berasal dari pemecahan fosfolipid membran sel oleh
ensim fosfolipase
• 5-lipoxygenase: menghasilkan leukotrien (LT)
• Cyclooxygenase (COX): Menghasilkan prostaglandin H2 (PGH2)
PGH2 merupakan substrat
pembentukan:
• Prostaglandin (PG)
• Thromboxan (Tx).

14. Metabolit AA dan perannya pada inflamasi.
Tanda silang merah menunjukkan target kerja obat anti inflamasi.
COX, cyclooxygenase; HETE, hydroxyeicosatetraenoic acid;
HPETE, hydroperoxyeicosatetraenoic acid.

15. Sintesis leukotrien and lipoxin oleh interaksi neutrofil dan platelet
AA: arachidonic acid –derived; LTA4: Leukotriene A4; LTC4:
Leukotriene C4

16. NITRIC OXIDE

17. Fungsi nitric oxide (NO) terhadap pembuluh darah dan
makrofag.
NO menimbulkan vasodilasi dan NO free radicals sangat toksik terhadap
mikroba dan sel mamalia. NOS: nitric oxide synthase.

18. IL-1 & Tumor Necrosis Factor (TNF)

19. Peran utama interleukin-1 (IL-1) dan tumor necrosis factor (TNF) pada inflamasi

20. COMPLEMENT

21. Complement Activation Pathways

22. Fungsi dan aktifasi complement system.
Ketiga jalur aktifasi complement bertemu di satu titik: pemecahan C3.

23. OXYGEN FREE RADICALS

24. Pembentukan reactive oxygen intermediates
dalam vesikel fagositik untuk membunuh
kuman

25. Saling keterkaitan 4 plasma mediator systems dipicu oleh aktifasi factor XII
(Hageman factor). Perhatikan bahwa thrombin menginduksi inflamasi setelah
berikatan dengan protease-activated receptors (terutama PAR-1) dari platelet,
endothelium, sel otot polos, dan sel lainnya.

26. Vasodilatation Prostaglandins
Nitric oxide
Histamine
Increased vascular permeability Vasoactive amines
C3a and C5a (through liberating amines)
Bradykinin
Leukotrienes C4, D4, E4
PAF
Substance P
Chemotaxis,
leukocyte recruitment and activation
C5a
Leukotriene B4
Chemokines
IL-1, TNF
Bacterial products
Fever IL-1, TNF
Prostaglandins
Pain Prostaglandins
Bradykinin
Tissue damage Neutrophil and macrophage lysosomal
enzymes
Oxygen metabolites
Nitric oxide
Peran Mediator pada inflamasi

27. Ringkasan peran Mediator radang akut
ACTION
Mediator Source Vascular Leakage Chemotaxis Other
Histamine and
serotonin
Mast cells, platelets + -
Bradykinin Plasma substrate + - Pain
C3a Plasma protein via liver + - Opsonic fragment (C3b)
C5a Macrophages + +
Leukocyte adhesion,
activation
Prostaglandins
Mast cells, from
membrane
phospholipids
Potentiate other
mediators
- Vasodilatation, pain, fever
Leukotriene B4 Leukocytes - +
Leukocyte adhesion,
activation
Leukotrienes
C4 D4 E4
Leukocytes, mast cells + -
Bronchoconstriction,
vasoconstriction
Platelet
Activating Factor
(PAF)
Leukocytes, mast cells + +
Bronchoconstriction,
leukocyte priming
IL-1 and TNF Macrophages, other - +
Acute-phase reactions,
endothelial activation
Chemokines Leukocytes, others - + Leukocyte activation
Macrophages,
endothelium
+ + Vasodilatation, cytotoxicity

28. Prostaglandin
Arachidonic acid
Eicosanoid
Eicosanoids
Leukotriene
Prostacyclin
Thromboxane
Thromboxane-A synthase
Essential fatty acid interactions
Leukotriene B4
Leukotriene E4
Prostacyclin synthase
Leukotriene A4
Leukotriene D4
Leukotriene C4
Thromboxane A2
Arachidonate 5-lipoxygenase
Prostaglandin H2
Prostaglandin E synthase
Arachidonic acid 5-hydroperoxide
Leukotriene C4 synthase
GLOSSARY abscess
acute inflammation
adhesion molecules
chemokinesis
chemotactic agent
chemotaxis
chronic inflammation
contact inhibition
degranulation
empyema
emigration
eosinophil
erosion
exudate
fibrin/fibrinous
fibrinogen
fibrous/fibrosis
free radicals
granulation tissue
granuloma
hyperemia
infection
keloid
left shift
leukocyte
leukemoid reaction
leukocytosis
lymphocyte
lysosomes
macrophage (AKA...)
margination
myeloperoxidase
neutrophil
neutrophilia
opsonization
organization
phagocytosis
plasma cell
pseudomembrane
purulent
pus
regeneration
resolution
scar
suppurate
transudate
ulcer