A novel canine leukointegrin, alpha d beta 2, is expressed by specific macrophage subpopulations in tissue and a minor CD8+ lymphocyte subpopulation in peripheral blood.
The beta 2 or leukointegrin family is comprised of three structurally related leukocyte surface heterodimers: LFA-1 (CD11a/CD18), Mac-1/Mo-1 (CD11b/CD18), and p150,95 (CD11c/CD18). In this work, we describe a novel canine beta 2 (CD18)-associated leukointegrin, designated alpha d. Expression of alpha d in tissues was prominent in macrophages in splenic red pulp, lymph node medullary regions, and bone marrow. In peripheral blood, alpha d expression was limited to a minor subpopulation of CD8+ T cells, which included small lymphocytes and large granular lymphocytes. A minor subpopulation of either CD8+ or CD4-CD8- splenic red pulp lymphocytes also expressed alpha d. Immunoprecipitation of alpha d from canine splenocytes revealed a heterodimer of 155 kDa and 95 kDa. Prior clearance of splenocyte extracts with an anti-CD18 mAb resulted in complete removal of alpha d. In addition, prior clearance of canine splenocyte extracts with anti-CD11a, anti-CD11b, or anti-CD11c mAb failed to clear alpha d. These immunoclearance data indicated that canine alpha d was antigenically distinct from the three known CD11 molecules, and occurred as an alpha d beta 2 heterodimer. Amino acid sequencing of canine alpha d affinity isolated from spleen further suggested that canine alpha d beta 2 probably represented a fourth member of the canine leukointegrin family via its homology to a subsequently discovered, novel human leukointegrin, alpha d beta 2, which further supported the uniqueness of the canine protein. The discovery of canine alpha d, and the demonstration of its highly restricted cell and tissue distribution, support a re-evaluation of leukointegrin-dependent inflammatory and immunologic interactions that involve cells now known to express alpha d.
Danilenko
D M
DM
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Rossitto
P V
PV
Van der Vieren
M
M
Le Trong
H
H
McDonough
S P
SP
Affolter
V K
VK
Moore
P F
PF
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry*; D004285:Dogs; D005434:Flow Cytometry; D016023:Integrins / Q000502:physiology*; D008264:Macrophages / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016023:Integrins; D013755:Tetradecanoylphorbol Acetate