Interaction of monocytoid cells with the mucosal addressin MAdCAM-1 via the integrins VLA-4 and LPAM-1.
The differentiation of myeloid cells into macrophages and granulocytes is accompanied by marked changes in adhesive phenotype. Here we seek to understand the regulation of expression and functionality of the VLA-4 (alpha 4 beta 1), LPAM-1 (alpha 4 beta 7) and HML-1 (alpha E beta 7) integrins on monocytes/macrophages and granulocytes, given that these integrins including LFA-1 (alpha L beta 2) mediate the entry, retention and signalling events of pathogenic leucocytes within chronically inflamed tissues. Phorbol ester-induced monocytic differentiation of the promyelocyte cell line HL60 led to increases in the steady-state levels of beta 2 and beta 7 mRNA transcripts, requiring a period of 10 and 24 h, respectively, of de novo protein synthesis. There was a parallel de novo expression of LPAM-1 on the cell surface, despite the fact that alpha 4 mRNA transcripts were rapidly down-regulated. At 72 h, HML-1 was not coexpressed with LPAM-1 on HL60 cells, although it was weakly expressed on peripheral blood monocytes/macrophages after a prolonged period of in vitro culture. Retinoic acid-induced granulocytic differentiation of HL60 cells led to the appearance of low levels of LPAM-1 at the cell surface. LPAM-1 was not found expressed on peripheral blood neutrophils, raising the possibility that it is transiently expressed during granulocyte differentiation. In accord with the above findings, differentiated monocytes and HL60 cells bound to recombinant MAdCAM-1 in an alpha 4- and beta 7-integrin-dependent fashion, whereas a population of undifferentiated HL60 cells and Mn(+2)-activated monocytes bound in an alpha 4-integrin-dependent beta 7-integrin-independent manner via VLA-4 expressed abundantly at all stages of differentiation. Four h after attachment, some of these VLA-4+ LPAM-1- HL60 cells could be seen to start spreading. These finding suggest that MAdCAM-1 can bind to VLA-4 when LPAM-1 is absent, and thus has the potential to recruit both VLA-4-bearing monocytes and VLA-4+ LPAM-1+ macrophages into chronically inflamed tissues.
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
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Yang
J E
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Harrison
C G
CG
Print
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Lehnert
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Sammar
A
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Lazarovits
G W
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Krissansen
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D018922:HL-60 Cells; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D039641:Integrin beta Chains; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D009088:Mucoproteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039041:Integrin alpha4beta1; D039641:Integrin beta Chains; D016023:Integrins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; C091368:integrin beta7; D039441:Integrin alpha4