The role of the leukocyte adhesion molecules VLA-4, LFA-1, and Mac-1 in allergic airway responses in the rat.
Chronic airway inflammation is involved in the pathogenesis of asthma. The leukocyte adhesion molecules VLA-4 of the beta 1 integrin family, and LFA-1 and Mac-1 of the beta 2 family have a demonstrated role in leukocyte-endothelial adherence and may play a role in airway inflammation in asthma. We studied the effects of blocking VLA-4 (CD49d/CD29) and both LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) airway responses and inflammation in rats. BN rats were sensitized with ovalbumin (OA) subcutaneously and were challenged 14 d later with aerosolized OA. Twelve rats were treated prior to challenge with anti-rat VLA-4 monoclonal antibody (mAb), 10 rats received both anti-LFA-1 and anti-Mac-1 mAb, and 14 rats received a control mAb. The pulmonary resistance (RL) was measured for 8 h after challenge. The inflammatory response was evaluated by bronchoalveolar lavage (BAL) and by measuring the lung and airway inflammatory cells retrieved by enzymative dispersion. The early response was significantly decreased in both the anti-VLA-4 group (131% baseline RL) and the anti-LFA-1/Mac-1 group (118%; p < 0.05) compared with the control group (202%). The late response was also significantly decreased in both the anti-VLA-4 (3.7) and anti-LFA-1/Mac-1 (2.6) groups compared with the control group (19.7). The significant differences in bronchoalveolar lavage were a decrease in neutrophils in the LFA-1/Mac-1 group and an increase in macrophages in the anti-VLA-4 group.(ABSTRACT TRUNCATED AT 250 WORDS)
Rabb
H A
HA
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Olivenstein
R
R
Issekutz
T B
TB
Renzi
P M
PM
Martin
J G
JG
D000403:Airway Resistance; D000485:Allergens; D000818:Animals; D000911:Antibodies, Monoclonal; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D016029:Receptors, Very Late Antigen / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology*
D000485:Allergens; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016029:Receptors, Very Late Antigen; D010047:Ovalbumin