Pediatric AIDS-associated lymphocytic interstitial pneumonia and pulmonary arterio-occlusive disease. Role of VCAM-1/VLA-4 adhesion pathway and human herpesviruses Academic Article uri icon

Overview

MeSH Major

  • AIDS-Related Opportunistic Infections
  • Arterial Occlusive Diseases
  • CD8-Positive T-Lymphocytes
  • Herpesviridae Infections
  • Lung Diseases, Interstitial
  • Vascular Cell Adhesion Molecule-1

abstract

  • Because the mechanisms of lymphocyte accumulation in the lungs of children with AIDS-associated lymphocytic interstitial pneumonia (LIP) are unknown, we studied the relative contributions of known adhesion pathways in mediating lymphocyte adherence to endothelium and the potential role of human herpesviruses in the expansion of these lesions. LIP was characterized by lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT) and infiltration of the pulmonary interstitium with CD8(+) T lymphocytes. In some individuals there was expansion of the alveolar septae with dense aggregates of B lymphocytes, many containing the Epstein-Barr viral (EBV) genome. Patients with concurrent EBV infection also demonstrated large-vessel arteriopathy characterized by thickening of the intimae with collagen and smooth muscle. Venular endothelium from the lung of children with LIP, but not uninflamed lung from other children with AIDS or lung from children with nonspecific pneumonitis, expressed high levels of vascular cell adhesion molecule-1 (VCAM-1) protein. In turn, inflammatory cells expressing very late activation antigen-4 (VLA-4), the leukocyte ligand for VCAM-1, were the predominant perivascular infiltrate associated with vessels expressing VCAM-1. Expression of other endothelial adhesion molecules, including intracellular adhesion molecule-1 and E-selectin, was not uniformly associated with LIP. Using a tissue adhesion assay combined with immunohistochemistry for VCAM-1, we show that CD8(+) T cell clones that express VLA-4 bind preferentially to pulmonary vessels in sites of LIP: vessels that expressed high levels of VCAM-1. When tissues and cells were pretreated with antibodies to VCAM-1 or VLA-4, respectively, adhesion was inhibited by >/=80%. Thus, infiltration of alveolar septae with CD8(+) T cells was highly correlative with VCAM-1/VLA-4 adhesive interactions, and focal expansion of B cells was coincidental to co-infection with EBV.

publication date

  • May 1999

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1866586

PubMed ID

  • 10329599

Additional Document Info

start page

  • 1453

end page

  • 64

volume

  • 154

number

  • 5