OM-85 BV upregulates the expression of adhesion molecules on phagocytes through a CD 14-independent pathway.
OM-85 BV is a preparation of bacterial extracts which proved to be of some efficacy in the prevention of respiratory tract infections. However, the mechanisms of action of this drug remain unclear. As we recently observed that OM-85 BV upregulates the expression of adhesion molecules on phagocytes, we took advantage of this property to determine whether the activating effects of OM-85 BV on monocytes and granulocytes depend on its interaction with CD14 molecules. Indeed, CD14 represents the major cell surface receptor for lipopolysaccharide and other bacterial products at the surface of leucocytes. First, we found that the upregulation of Mac-1 (CD11b/CD18) induced in vitro by OM-85 BV on monocytes was not blocked by an anti-CD14 monoclonal antibody (mAb) which inhibits monocyte responses to lipopolysaccharide. Similarly, the anti-CD14 mAb inhibited upregulation of Mac-1 on granulocytes when it was induced by lipopolysaccharide but not by OM-85 BV. To confirm that the effects of OM-85 on the expression of Mac-1 is CD14-independent, we analysed the responses of a patient with paroxysmal nocturnal haemoglobinuria, a disease associated with a defect of CD14 expression at the membrane of phagocytes. We found that monocytes and granulocytes of this patient displayed an impairment in Mac-1 upregulation in response to lipopolysaccharide whereas they responded normally to OM-85 BV. We conclude that OM-85 BV activates phagocytes through a CD14-independent pathway. The characterisation of the cell surface receptors of monocytes and granulocytes involved in the interactions with OM-85 BV might provide a molecular clue to the mode of action of this preparation of bacterial extracts.
Hôpital Erasme, Department of Immunology, Université Libre de Bruxelles, Belgium.
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Marchant
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Goldman
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial; D001419:Bacteria; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002457:Cell Extracts; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*; D000095983:Bacterial Lysates
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015815:Cell Adhesion Molecules; D002457:Cell Extracts; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D011837:Radiation-Protective Agents; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates; C050501:OM 89