Macrophage procoagulant-inducing factor. In vivo properties and chemotactic activity for phagocytic cells.
Murine macrophage procoagulant-inducing factor (MPIF) is a lymphokine with chemical properties distinct from a number of well-characterized cytokines. MPIF induces procoagulant activity on the surface of macrophages and thus may play a central role in the expression of cell-mediated immunity. Highly enriched MPIF-alpha and -beta, separated by virtue of their basic isoelectric point and affinity for heparin, induced local induration and fibrin deposition and cellular infiltration similar to that observed in delayed type hypersensitivity reactions, when injected intradermally. Margination with of polymorphonuclear leukocytes (PMN) along the endothelium as well as increased PMN infiltration was evident after 4 h. In contrast to other inflammatory mediators (e.g., C5a, IL-1) reactivity was sustained, with greater numbers of mononuclear cells apparent 24 h after skin testing. Changes in the dermis were evident 4 h after MPIF injection with increased numbers of cells near areas where spaces in the collagen bundles had formed. Dermal thickening was evident after 24 h and collagen fiber structure was disrupted. Extravascular fibrinogen/fibrin was most prominent 24 h after testing. LPS, which induces macrophage procoagulant activity in vitro, did not induce the histopathologic changes evident with MPIF. MPIF was chemotactic for PMN and macrophages in vitro. Chemotactic activity was heat-labile and not due to C5a. Migration was dependent on a concentration gradient, as determined by checkerboard analysis, indicating that MPIF promoted chemotaxis rather than chemokinesis. Experiments reported here suggest that MPIF is an important mediator of fibrin deposition and cellular infiltration characteristic of cell-mediated immune response.
Ryan
J
J
Kolling Institute of Medical Research, St. Leonards, N.S.W., Australia.
Geczy
C L
CL
D000818:Animals; D001202:Ascitic Fluid; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000502:physiology*; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000473:pathology; D012882:Skin Tests
D001779:Blood Coagulation Factors; D002630:Chemotactic Factors; C045072:macrophage procoagulant activity