Human lung mast cells adhere to human airway smooth muscle, in part, via tumor suppressor in lung cancer-1.
Mast cells infiltrate the airway smooth muscle (ASM) of patients with asthma, an event which is likely to be a key factor in the development of this disease. Adhesion is a fundamental mechanism facilitating cellular cross-talk. We have examined whether human lung mast cells (HLMC) and ASM adhere, and have also examined the mechanism involved. Primary cultures of HLMC and confluent human ASM were cocultured for 30 min, then nonadherent HLMC were removed by centrifugation. HLMC adhered avidly to ASM monolayers (mean +/- SEM adhesion 43.2 +/- 1.2%, n = 41). Adhesion was increased to 58.8 +/- 2.7% by 1 mM Mn2+ (p = 0.015), and was reduced by EDTA and EGTA to 20.5 +/- 1.5% and 21.0 +/- 1.3%, respectively (p < 0.0001). Adhesion-blocking Abs for ICAM-1, VCAM-1, CD18, and the alpha4 and beta1 integrins had no effect on HLMC adhesion. HLMC expressed tumor suppressor in lung cancer-1 (TSLC-1) and blocking this reduced adhesion from 38.5 +/- 4.8% to 28.3 +/- 3.7% (p = 0.004, n = 7). ASM did not express TSLC-1, indicating that TSLC-1 acts as a heterophilic adhesion molecule. In summary, HLMC adhere avidly to ASM in part via TSLC-1 and in part via an as-yet-undefined Ca2+-dependent pathway. This supports the hypothesis that adhesion is important in the recruitment and retention of HLMC by the ASM in asthma, and for the functional interaction of these cells.
Yang
Weidong
W
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom.
Kaur
Davinder
D
Okayama
Yoshimichi
Y
Ito
Akihiko
A
Wardlaw
Andrew J
AJ
Brightling
Christopher E
CE
Bradding
Peter
P
D001249:Asthma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020013:Calcium Signaling; D002448:Cell Adhesion / Q000502:physiology*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000166:cytology* / Q000503:physiopathology; D008407:Mast Cells / Q000166:cytology* / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology* / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins