Leukocyte Extravasation - Pathology

Overview

                        Introduction
                    
                        Leukocytes play an important role in eliminating offending agents
                    
                        neutrophils and macrophages are capable of destroying microbes, necrotic tissue, and foreign substances
                    
                        The process of leukocytes migrating from the blood vessel to tissue involves multiple steps and are mediated by adhesion molecules and chemokines
                    
                        margination
                    
                        leukocytes become redistributed closer to the vessel wall
                    
                        rolling
                    
                        leukocytes transiently attach to endothelium and then detach
                    
                        these cells therefore "roll" on the vessel wall
                    
                        the endothelium possesses E-selectin and P-selectin
                    
                        cytokines from the inflamed tissue regulate selectin expression
                    
                        Sialyl-Lewis X protein binds to E-selectin and P-selectin
                    
                        found on leukocytes
                    
                        firm endothelial adhesion
                    
                        mediated by integrin proteins
                    
                        vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule-1 (ICAM-1) are found on the endothelium
                    
                        low affinity integrin are found on leukocytes
                    
                        migration through the vessel wall
                    
                        migration to tissue
                    
                        StepMolecule on Vasculature/StromaMolecule on Leukocyte
1. Loose adhesion, rolling
 E-selection, P-selectin
Sialyl Lewis
2. Tight adhesion ICAM-1
LFA-1 (integrin)
3. Diapedesis PECAM-1PECAM-1
4. Migration through ECMBacterial products, C5a, IL-8, LTB4, KallikreinVarious

Action	Numeric Key	Letter Key	Function Key
Show Bullets		S	Enter (frontside only)
20%	1	N
40%	2	H
60%	3	F	Enter (backside only)
80%	4	E
100%	5	M
Toss	0	T

Step	Molecule on Vasculature/Stroma	Molecule on Leukocyte
1. Loose adhesion, rolling	E-selection, P-selectin	Sialyl Lewis
2. Tight adhesion	ICAM-1	LFA-1 (integrin)
3. Diapedesis	PECAM-1	PECAM-1
4. Migration through ECM	Bacterial products, C5a, IL-8, LTB4, Kallikrein	Various