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Relationship between murine macrophage Fc receptor-mediated phagocytic function and competency for activation for non-specific tumor cytotoxicity

, : Relationship between murine macrophage Fc receptor-mediated phagocytic function and competency for activation for non-specific tumor cytotoxicity. Immunobiology 171(3): 220-233

The relationship between Fc receptor (FcR) function and activation of murine macrophage populations for non-specific tumor cytotoxicity was studied. Oil-elicited inflammatory peritoneal macrophages (PM phi) from C3HeB/FeJ mice had higher FcR function upon harvest than resident PM phi from the same strain or elicited PM phi from genetically deficient C3H/HeJ mice. C3HeB/FeJ inflammatory PM phi were uniformly responsive to activation by MAF and the complement activators: LPS, Poly I:C, cobra venom factor (CVF) and zymosan for tumoricidal activity. Resident cells from the same strain and C3H/HeJ-elicited PM phi were uniformly unresponsive to the same activators. In vitro culture of C3HeB/FeJ resident PM phi with fetal bovine serum for 24-48 h produced unregulation of FcR function which coincided with a conversion from an unresponsive to a responsive state for tumoricidal activity. Reconstitution of the FcR function of C3H/HeJ-elicited PM phi during 24-48 h culture with lymphokine or Poly I:C also coincided with the restoration of responsiveness to activation by LPS, CVF, and zymosan for tumor cytotoxicity. Thus, the consistent temporal relationship between upregulated FcR function and the capacity of macrophages to respond to activation for non-specific tumoricidal activity may be more than coincidental. Preincubation of responsive C3HeB/FeJ-elicited PM phi with insoluble immune complex or heat-aggregated IgG was shown to blockade FcR-mediated phagocytosis and to abrogate LPS-mediated tumoricidal activity. Interestingly, FcR blockade by IgG-opsonized sheep erythrocyte conjugates selectively inhibited activation by MAF, LPS, and Poly I:C, but had no inhibitory effect on activation by CVF or zymosan. Similar blockade of C3b receptors produced an identical pattern of selective inhibition of activation. This selective inhibition of non-specific tumoricidal activity by FcR/C3bR blockade suggests the existence of two pathways for antibody-independent activation of macrophages.

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Accession: 041221594

PMID: 3519439

DOI: 10.1016/S0171-2985(86)80006-7

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