Novel cell surface adhesion receptors involved in interactions between stromal macrophages and haematopoietic cells

Abstract

SummaryImmunocytochemical staining of tissues with the mouse macrophage-specific monoclonal antibody, F4/80, has shown that large numbers of stromal macrophages are present in adult and foetal haematopoietic tissues. Macrophage plasma membrane processes are seen to establish extensive associations with myeloid and erythroid cells in adult bone marrow and with developing erythroblasts in foetal liver, suggestive of local trophic interactions. To explore the nature of these interactions, methods were developed for isolation of resident bone marrow macrophages (RBMM) and foetal liver macrophages (FLM). Following collagenase digestion of bone marrow or foetal liver, clusters were obtained which were composed of one or more central macrophages surrounded by proliferating haematopoietic cells. After attachment of clusters to glass coverslips, adherent macrophages could be stripped free of haematopoietic cells by pipetting in the absence of divalent cations. The purified RBMM, but not FLM, expressed a novel haemagglutinin, which mediated binding, without ingestion, of large numbers of unopsonized sheep erythrocytes by a divalent cation-independent mechanism. In view of the possibility that this sheep erythrocyte receptor (SER) could interact with a homologous ligand on mouse bone marrow cells, its properties were examined. SER was found to be a lectin-like protein which recognized protease-resistant sialylated glycoconjugates on sheep erythrocytes. The expression of SER was restricted to certain stromal tissue macrophages and was low or absent on monocytes and macrophages obtained from serous cavities. High levels of SER could be induced on elicited peritoneal macrophages by cultivation in mouse serum and the induced receptor was found to mediate low-avidity binding of murine bone marrow cells with characteristics indistinguishable from those seen for binding of sheep erythrocytes. However, maximal binding of bone marrow cells to RBMM depended on a distinct, divalent cation-dependent adhesion system. Using erythroblasts as a ligand, FLM were selected to explore the properties and expression of this adhesion receptor, the erythroblast receptor (EbR). Similar to SER, EbR did not mediate ingestion, and was restricted in its expression to foetal and adult stromal tissue macrophages. Unlike SER, EbR activity was not affected by neuraminidase treatment of the ligand and the receptor was not induced on peritoneal macrophages cultured in mouse serum. EbR appears to be a novel cell adhesion receptor because it was unaffected by inhibitors of several previously described cell adhesion molecules, including the fibronectin receptor. Future studies will attempt to explore the functional significance of these two receptors in macrophage-haematopoietic cell interactions.

Interleukin 4 regulates induction of sialoadhesin, the macrophage sialic acid-specific receptor.

“…Distinct hemagglutinins appear to be important in the attachment ofmyeloid and erythroid precursors to bone marrow macrophages via sialoadhesin and a divalent cation-dependent adhesion receptor (22). Our present results show that IL4 is highly selective in its downmodulation of sialoadhesin and other, unpublished observations show that IL4 does not influence divalent cation-dependent erythroblast-binding activity.…”

The macrophage: Past, present and future

“…Non-phagocytic contact-dependent interactions involving macrophages and other cells have not received sufficient attention, but their trophic activities could play an important role in haematopoiesis within the bone marrow stroma [72], in homeostasis within the neuro-endocrine system [15] and in the evolution of tumours [25], where TAM are able to promote malignancy as well as influencing tumour cell migration and metastasis. The possibility that surface contact-dependent interactions can contribute directly to cellular and antimicrobial cytoxicity, without antibody involvement or phagocytosis, should also be considered.…”

Innate immune cells as homeostatic regulators of the hematopoietic niche

“…These cells were later confirmed to be macrophages by immunoreactivity with the F4/80 antibody [28]. Although these initial studies already noted intimate contacts between macrophages and various components of the BM, they failed to provide insights into their functions in this organ.…”