Studies on the fibronectin receptors of human peripheral blood leukocytes. Morphologic and functional characterization.

Abstract

We have investigated the interactions between plasma fibronectin (Fn) and human peripheral blood phagocytic cells. As shown by studies of the binding of Fn-coated fluorescent microspheres (Fn-ms), both polymorphonuclear leukocytes (PMN) and monocytes had specific binding sites for Fn at the plasma membrane. However, as purified from blood, only monocytes were stimulated by Fn to become more actively phagocytic. This increase in phagocytosis was reflected by an Fn-induced increase in the ingestion of IgG-coated erythrocytes and, more dramatically by an Fn-dependent initiation of phagocytosis of C3b-coated erythrocytes. Despite this difference between PMN and monocytes in the functional consequences of Fn binding, the cell surface molecules responsible for Fn binding on the two cell types shared many characteristics. On both cells, binding of Fn-ms was inhibited by sufficient concentrations of fluid-phase Fn; both PMN and monocytes bound fewer Fn-ms at 4 degrees C than at 37 degrees C; both achieved maximal binding at similar Fn-ms/cell ratios; and phenylmethylsulfonyl fluoride did not inhibit Fn-ms binding to either cell type. Most dramatically, monoclonal anti-Fn antibodies that inhibited binding of Fn-ms to one cell type inhibited binding to both; conversely, monoclonal anti-Fn antibodies that did not inhibit Fn-ms binding to either cell type did not inhibit binding to the other. Fn will stimulate PMN to a more actively phagocytic state, like that induced in monocytes, if the PMN are first exposed to C5a or N-formyl-methionyl-leucylphenylalanine. This effect occurs without apparent change in the number of Fn receptors. We conclude that the PMN and monocyte receptors for Fn are very similar, but that their milieu is very different in the two cells as purified from peripheral blood. Whereas Fn induces increased phagocytosis in monocytes, PMN must be activated before the Fn can be effective.

Induction of neutrophil respiratory burst by tumour necrosis factor-alpha; priming effect of solid-phase fibronectin and intervention of CD 11b-CD18 integrins

“…in this regard, neutrophils exposed to MoAbs during induction of adherence, and then washed to remove nonadherent eells and unbound MoAbs, displayed an immediate response to TNF-a. Consequently, it appears that: (i) the priming of neutrophils by KN is mediated by surfaee structures dislinet from CDllb-CDi8, possibly related to FN receptors [20,21]. Nevertheless, the identification of these structures with molecules involved in the promotion of the cell adherence to FN remains to be established; (ii) the activation ofthe respiratory burst of these adherent cells can be ablated by re-adding MoAbs together with TNF-a.…”

Leukocyte adhesion-deficient neutrophils fail to amplify phagocytic function in response to stimulation. Evidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis.

“…Stimulation of PMN with various inflammatory mediators markedly augments both Fc-and CR1-mediated ingestion (1)(2)(3)(4)(5)(6)(7)(8)(9). This recruitment of phagocytic function is reflected not only in the total number of ingested targets but also in the percentage of PMN participating in the phagocytic process (1,2). Presumably, this regulation of ingestion acts to limit the damaging products of PMN activation, such as toxic oxygen metabolites and secreted lysosomal products, to the site of inflammation.…”

“…Despite its central role in host defense, knowledge of the regulation of phagocytic function at inflammatory sites has lagged behind understanding of activation of the respiratory burst and exocytosis, other func-tions of professional phagocytes required for the maintenance of homeostasis. Recent investigations from our group into the regulation of human neutrophil (PMN) phagocytosis have led us to hypothesize that phagocytosis by PMN is primarily a recruited function at inflammatory sites (1)(2)(3)(4)(5). Stimulation of PMN with various inflammatory mediators markedly augments both Fc-and CR1-mediated ingestion (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

“…Recent investigations from our group into the regulation of human neutrophil (PMN) phagocytosis have led us to hypothesize that phagocytosis by PMN is primarily a recruited function at inflammatory sites (1)(2)(3)(4)(5). Stimulation of PMN with various inflammatory mediators markedly augments both Fc-and CR1-mediated ingestion (1)(2)(3)(4)(5)(6)(7)(8)(9). This recruitment of phagocytic function is reflected not only in the total number of ingested targets but also in the percentage of PMN participating in the phagocytic process (1,2).…”

“…We and others have found that PMN can recruit several distinct molecular mechanisms for phagocytosis in response to inflammatory signals, which may be regulated further by the specific opsonin (IgG, C4b, C3b, and C3bi) and opsonin receptor (FcRII, FcRIII, CR1, and CR3) engaged (1)(2)(3)(4)(5)(6)(7)(8)(9). In addition, monocytes and macrophages employ quite different molecular mechanisms for phagocytosis from those employed by PMN, even when the same opsonin or opsonin receptor is involved (1,10).…”