Novel anti-inflammatory compounds prevent CD11b/CD18, alpha M beta 2 (Mac-1)-dependent neutrophil adhesion without blocking activation-induced changes in Mac-1.
Leumedins are small organic molecules with anti-inflammatory properties in vivo. We report here that leumedins inhibit the CD11b/CD18 alpha M beta 2 (Mac-1)-dependent adherence of neutrophils to serum proteins. The activation of neutrophils leading to adherence via Mac-1 is associated with an increase in cell surface Mac-1 level, and with an increased affinity of Mac-1 for adhesion partners. Inhibition of neutrophil adherence by leumedins does not require blocking the recruitment of Mac-1 from intracellular granules to the cell surface. Furthermore, leumedins do not block the expression on Mac-1 of the epitope for an "activation-specific" antibody (CBRM1/5). Time course studies show that leumedins inhibit adherence by targeting an event which occurs concurrently with changes in Mac-1 level and induction of the CBRM1/5 epitope. Therefore, leumedins block an unknown process which is permissive for Mac-1-dependent adherence.
Endemann
G
G
Scios Nova Inc., Mountain View, California, USA.
Feng
Y
Y
Bryant
C M
CM
Hamilton
G S
GS
Perumattam
J
J
Mewshaw
R E
RE
Liu
D Y
DY
D000595:Amino Acid Sequence; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D000939:Epitopes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D000939:Epitopes; D007476:Ionophores; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D007930:Leucine