• AlphaM integrin chain
• AlphaM-beta2
• C3biR
• CR3
• Mac-1
• Mo1

MAJOR LINKS FOR CD11b  

• NCBI LocusLink Record: 3684
• Mendelian Inheritance in Man (OMIM): 120980
• SwissProt annotated protein record: P11215

CELLULAR FUNCTION OF CD11b  

• Neutrophil and monocyte interactions with stimulated endothelium;
• Phagocytosis of iC3b or IgG coated particles*
• Neutrophil respiratory burst or degranulation stimulated by other receptors eg. FcR or C5a and channeled through CD11b/CD18*
• Spreading**
• Chemotaxis**
• Apoptosis**

DISEASE RELEVANCE OF CD11b AND FUNCTION OF CD11b IN INTACT ANIMAL  

• Absent in Leukocyte Adhesion Deficiency (LAD-1) patients who have major problems with bacterial infections*
• Target of anti-inflammatory drug therapeutics**

• Families in which CD11b is a member
  • CD11b-->integrin alpha chains-->integrin assemblies

MOLECULAR STRUCTURE OF CD11b  

• Type 1 transmembrane protein
• 1136 or 1137 amino acids*
• 1091 or 1092 residue extracellular region*
• 26 residue transmembrane region
• 19 residue cytoplasmic region
• A major ligand binding site has been mapped to a von Willebrand A domain (I domain) which is inserted between repeats two and three. The structure of this CD11b I domain has been solved and shown to resemble a classic [alpha]-[beta] dinucleotide binding fold (Lee et al. 1995). The seven repeating domains (I-VII) of the integrin alpha subunit have been modeled to resemble a [beta] propeller fold (Springer 1997)

MOLECULAR MASS OF CD11b  

POST-TRANSCRIPTIONAL MODIFICATION OF CD11b  

• An extra codon (CAG) between bp 1580 and 1581 is found in some CD11b cDNAs**
• Genomic sequencing revealed that this codon forms the last three bases of the intronic acceptor located between exons 13 and 14 of CD11b, suggesting alternative splicing**
• Receptors with or without the extra codon are functionally indistinguishable**

POST-TRANSLATIONAL MODIFICATION OF CD11b  

• 19 potential N-glycosylation sites

SUBSTRATES FOR CD11b   - No information

ENZYMES WHICH MODIFY CD11b   - No information

LIGANDS FOR CD11b AND MOLECULES ASSOCIATED WITH CD11b  

• Binding site for some ligands such as iC3b, ICAM-1 (CD54), ICAM-2 (CD102), and fibrinogen is in the A (I) domain
• The structural basis for many of the reported CD11b/CD18 ligands is presently unclear

• Granulocytes
• Monocytes
• NK cells
• Subset of T cells
• Subsets of B cells

SELECTION OF OTHER CD11b-SPECIFIC REFERENCE MAB  

REVIEWS

1. Arnaout MA Leukocyte adhesion molecules deficiency: its structural basis, pathophysiology and implications for modulating the inflammatory response. Immunol Rev 1990 114:145 ** PubMed

2. Petty HR,Todd RF 3d Integrins as promiscuous signal transduction devices. Immunol Today 1996 17:209 PubMed

3. Springer TA Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994 76:301 PubMed

4. Stewart M,Thiel M,Hogg N Leukocyte integrins. Curr Opin Cell Biol 1995 7:690 PubMed

PRIMARY CITATIONS

5. Arnaout MA,Gupta SK,Pierce MW,Tenen DG Amino acid sequence of the alpha subunit of human leukocyte adhesion receptor Mo1 (complement receptor type 3). J Cell Biol 1988 106:2153 ** PubMed

6. Corbi AL,Kishimoto TK,Miller LJ,Springer TA The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B. J Biol Chem 1988 263:12403 PubMed

7. Coxon A,Rieu P,Barkalow FJ,Askari S,Sharpe AH,von Andrian UH,Arnaout MA,Mayadas TN A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity 1996 5:653 ** PubMed

8. Diamond MS,Garcia-Aguilar J,Bickford JK,Corbi AL,Springer TA The I domain is a major recognition site on the leukocyte integrin Mac- 1 (CD11b/CD18) for four distinct adhesion ligands. J Cell Biol 1993 120:1031 PubMed

9. Lee JO,Rieu P,Arnaout MA,Liddington R Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). Cell 1995 80:631 PubMed

10. Michishita M,Videm V,Arnaout MA A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding. Cell 1993 72:857 PubMed

11. Springer TA Folding of the N-terminal, ligand-binding region of integrin alpha- subunits into a beta-propeller domain. Proc Natl Acad Sci U S A 1997 94:65 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/15/99   mpr@mail.nih.gov