Related Experiment Video

Updated: Aug 24, 2026

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin
13:45

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin

Published on: December 23, 2010

The role of alpha 4 integrins in lung pathophysiology

R R Lobb1, B Pepinsky, D R Leone

  • 1Biogen Inc., Cambridge Center, MA 02142, USA.

The European Respiratory Journal. Supplement
|August 1, 1996
PubMed

Insights

Monoclonal antibodies targeting alpha 4 integrins block eosinophil and T-cell recruitment, reducing airway hyperresponsiveness. This suggests alpha 4 integrin antagonists could be novel therapeutics for asthma.

Area of Science:

  • Immunology
  • Cell Biology
  • Respiratory Medicine

Background:

  • Alpha 4 integrins are crucial leukocyte cell surface molecules mediating cell-matrix adhesion.
  • Integrin alpha 4 beta 1 binds VCAM-1 and fibronectin; alpha 4 beta 7 binds VCAM-1, fibronectin, and MAdCAM.

Purpose of the Study:

  • To investigate the role of alpha 4 integrins in allergic airway inflammation.
  • To determine the mechanism of action of monoclonal antibody HP1/2 in blocking alpha 4 integrin function.

Main Methods:

  • Utilized monoclonal antibodies (MoAbs) against alpha 4 integrins.
  • Conducted in vitro adhesion assays and in vivo lung antigen challenge models in sheep.
  • Generated and tested Fab fragments of MoAb HP1/2.

Main Results:

  • MoAbs blocked alpha 4 integrin adhesive function in vitro.
  • In vivo studies showed alpha 4 integrins are key in eosinophil/T-cell recruitment and airway hyperresponsiveness.
  • MoAb HP1/2 (intact or Fab fragments) was efficacious in a sheep allergic airways model, demonstrating blockade of adhesive function.

Conclusions:

  • The in vivo efficacy of MoAb HP1/2 is due to direct blockade of alpha 4 integrin adhesive function.
  • Alpha 4 integrins are critical targets for managing allergic airway inflammation.
  • Humanized monoclonal antibodies or other alpha 4 integrin antagonists show therapeutic potential for asthma.

More Related Videos

Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis07:52

Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis

Published on: December 21, 2014

Advanced Imaging of Lung Homing Human Lymphocytes in an Experimental In Vivo Model of Allergic Inflammation Based on Light-sheet Microscopy10:39

Advanced Imaging of Lung Homing Human Lymphocytes in an Experimental In Vivo Model of Allergic Inflammation Based on Light-sheet Microscopy

Published on: April 16, 2019

Related Concept Videos

Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Chronic Obstructive Pulmonary Disease-II: Pathophysiology01:20

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Asthma-II: Pathophysiology and Classification01:26

Asthma-II: Pathophysiology and Classification

Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
Asthma I: Introduction01:28

Asthma I: Introduction

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow obstruction and heightened bronchial responsiveness to a wide range of triggers. The underlying inflammation leads to airway swelling, mucus hypersecretion, and smooth muscle constriction, all of which narrow the airway lumen and impede airflow. Clinically, asthma presents with recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing, symptoms that typically vary in intensity and...