Introduction to ‘Inflammation’ Dr. habil. Kőhidai László Assoc. Professor Dept. Genetics, Cell- and Immunobiology Semelweis University Chemotaxis - Elective Course 2016– EM-ED

Components of inflammatory response Cells of connective tissue Vascular lumen Extracellular matrix Collagen IV. Laminin Fibronectin Elastin Proteoglycan

Inflammation phase 1 contraction of endothel histamine, bradykinin

Inflammation phase 2 injury of endothel bacterial, burns 2-12 hrs

Inflammation phase 3 accumulation of leukocytes release of proteolytic enzymes

Inflammation phase 4 regeneration of capillaries

Activation of endothel PAF P selectin Cytokine NO IL-8 E selectin PAF = platelet activating factor

Most significant groups of chemoattractant substances in inflammation Soluble bacterial products (e.g. fMLF) Products of complemet cascade (e.g. C5a) Arachidonic acid metabolism – products of lipoxigenase line (LTB4)

Ag-Ab complex C1 C3 C4+C2 B C1a C3b D C4bC2a C3 C3bBb C4bC2aC3b C3a C3b C5 C3bBb3b C5a C5b Alternative pathway Classical pathway C5-9 Membrane attack complex

Plasma origin chemoattractant substances Complement C3a C4a C5a C5a desArg Fibrinogen fibrinopeptide B D E

Arachidonic acid metabolites Phospholipides of surface membrane Phospholipases ARACHIDONIC ACID lipoxigenase cyclooxygenase Leukotrien A4 (LTA4) Prostaglandin G2 (PGG2) PGH2 PGD2 PGE2 PGF2a LTC4 LTD4 LTE4 LTB4

Characterization of cytokines small molecular mass, glycisilated proteins members of inflammatory and immune processes short lifespan auto- and paracrine actions significant effects even in low concentrations inducers of RNA and protein synthesis in the target cells frequent inducer and blocker crossreactions transmodulation on receptors of each other

IL-1 TNF Producer and target cells of cytokines granulocyte lymphocyte macrophage keratinocyte astrocyte mezangial cell macrophage NK-cell mast cell IL-1 TNF granulocyte lymphocyte + vascular responses

IL-1 TNF IL-8 synthesis Inducer crossreactions between cytokines monocyte macrophage fibroblast endothel epithel IL-8 synthesis Inducer crossreactions between cytokines

Neutrophil-dependent C5a M TNF IL-1 U U U Endothel-dependent

Diversity of dynamism in migration of different cells 24 48 (hrs) monocytes neutrophils cell number Acute phase