CD18 deficiency protects against multiple low-dose streptozotocin-induced diabetes.
Leukocyte recruitment into pancreatic islets is believed to play an important pathophysiological role in autoimmune diabetes. Previous reports have suggested that several different adhesion molecules may be involved in leukocyte recruitment during autoimmune diabetes, including members of the leukocyte beta(2) integrins. Here we report that a gene-targeted deficiency of the beta(2) integrin, CD18, protects against multiple low-dose streptozotocin-induced autoimmune diabetes. CD18 null mice displayed lower blood glucose values throughout the study, with only 10% of these mice eventually developing diabetes compared to 95% in the control group. Importantly, the development of insulitis was markedly absent in the CD18 null mice, suggesting that members of this integrin subfamily predominately regulate leukocyte infiltration into pancreatic islets. This study demonstrates that the beta(2) integrins play a key pathophysiological role in the development of multiple low-dose streptozotocin-induced autoimmune diabetes.
Barlow
Shayne C
SC
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Langston
Will
W
Matthews
Kametra M
KM
Chidlow
John H
JH
Kevil
Christopher G
CG
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018821:CD18 Antigens / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D018390:Gene Targeting; D006943:Hyperglycemia / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D001786:Blood Glucose; D018821:CD18 Antigens