The role of protected extracellular compartments in interactions between leukocytes, and platelets, and fibrin/fibrinogen matrices.
Polymorphonuclear leukocytes express multiple surface receptors that mediate their adhesion to extracellular matrices and to other cells. These receptors also play roles in cell migration and phagocytosis. We have studied the role of one class of polymorphonuclear leukocytes surface receptors, the beta 2 integrins, in the interactions of these cells with fibrinogen. We have found that the beta 2 integrins, CD11b/CD18 (complement receptor three) and CD11c/CD18 mediate attachment of polymorphonuclear leukocytes to fibrinogen-coated surfaces. Polymorphonuclear leukocytes must be stimulated with chemoattractants, such as fMLP, or with cytokines, such as tumor necrosis factor to bind to fibrinogen via these integrins. Moreover, each of these integrins interacts with a different segment of the fibrinogen molecule. PMN adherence to fibrinogen via CD11b/CD18 depends on the carboxy terminus of fibrinogen, whereas adherence via CD11c/CD18 depends on the amino terminus of fibrinogen's alpha-chain. One of the physiological consequences of these interactions is that polymorphonuclear leukocytes stimulated with either chemoattractants or TNF form protected compartments at their interface with fibrinogen-coated surfaces and that elastase released into these compartments is inaccessible to protease inhibitors present in the plasma. These protected compartments exclude plasma proteins of > 40,000 daltons such as alpha 1 anti-proteinase, thereby allowing polymorphonuclear leukocyte proteases to degrade matrix proteins within this compartment without interference by plasma anti-proteinases.
Loike
J D
JD
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Silverstein
R
R
Wright
S D
SD
Weitz
J I
JI
Huang
A J
AJ
Silverstein
S C
SC
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*
D016023:Integrins; D005337:Fibrin; D005340:Fibrinogen