The alpha4beta1 integrin can mediate leukocyte adhesion to casein and denatured protein substrates.
An understanding of the binding specificity of leukocyte integrins is important to determine the range of ligands that interact with these receptors during inflammatory processes. In this study we show that the alpha4beta1 integrin can interact with casein and denatured albumin and promote leukocyte adhesion through these interactions. This was demonstrated with the use of blocking antibodies directed to alpha4beta1 and peptide adhesion competitors containing the alpha4beta1 binding tripeptide, Leu-Asp-Val (LDV). Consistent with this data, the adhesion is completely divalent cation-dependent and is stimulated by known activators of leukocyte integrin function, namely phorbol ester and the beta1 integrin activating antibody, 8A2. It is interesting to note that neither bovine alpha-casein or human albumin contain an LDV site (present in the CS-1 site of alternatively spliced fibronectin) or an IDS site (present in VCAM-1) yet they promote adhesion through this integrin. Furthermore, alpha4beta1 directly binds to Sepharose columns containing casein, casein fragments, or denatured albumin but does not bind columns containing native albumin. These data suggest that the binding specificity for the alpha4beta1 integrin is considerably broader than previously realized. This work has implications for how subsets of leukocytes may interact with damaged proteins during tissue injury and inflammation.
Davis
G E
GE
Department of Pathology, Texas A & M University Health Science Center, College Station 77843-1114, USA.
Thomas
J S
JS
Madden
S
S
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001667:Binding, Competitive; D002364:Caseins / Q000378:metabolism; D002413:Cations, Divalent; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D039441:Integrin alpha4; D019012:Integrin beta1 / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D011489:Protein Denaturation; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D002364:Caseins; D002413:Cations, Divalent; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D010455:Peptides; D039441:Integrin alpha4