Kim E. Longworth, Ph.D.

Department of Surgical and Radiological Sciences, School of Veterinary Medicine University of California, Davis, CA

Received 4/11/97; Accepted 5/21/97

2. INTRODUCTION

Pulmonary intravascular macrophages are a distinct population of cells that permanently reside within the pulmonary capillaries of some species of mammals. Research on the physiological significance of these cells has only developed in the last 10 years. However, it is clear from this research that, in species that have them, the macrophages play an important role in the animal's response to some invading pathogens, endotoxin or foreign particles (1-7).

Since 1988, reviews (1, 2, 3, 4, 5) a monograph (6) and a book chapter (7) have focussed on various aspects of pulmonary intravascular macrophage biology. As the first publication of this topic to be presented in an electronic forum, this review will emphasize some of the key features of the anatomy and physiology of these cells that were touched upon in published reviews.

The mononuclear phagocyte system in mammals is comprised of phagocytic cells throughout the body responsible for removing particles from the circulation (8, 9). The liver has historically been regarded as the functional center of that system because of the Kupffer cells (stellate macrophages) lining its sinusoids and because of the high fraction of systemic blood flow (about 20%) that it receives. The spleen and bone marrow, with their associated macrophage populations, are secondary sites for particle clearance, mainly because their blood flows are low.

This hepatic orientation of regional phagocytosis is based on studies in typical laboratory mammals, and humans (9, 10). Early studies showed that intravenously injected foreign particles are mostly retained by the liver and spleen in rats, rabbits and dogs (11, 12). However, although these studies suggested that the lung could retain a substantial fraction of blood-borne particles in some species, this observation was largely ignored for many decades (1). More recently, the macrophages responsible for lung retention of particles were considered to be displaced Kupffer cells by Schneeberger-Keeley and Burger (13), but later were formally identified as a resident population of macrophages by Rybicka et al. (14). Later studies confirmed the pulmonary orientation of phagocytosis in sheep, pigs, cats and calves (15, 16, 17, 18, 19).

The mononuclear phagocyte system of the lung is comprised of cells in 3 compartments; airway and alveolar macrophages, interstitial macrophages and, in some species, intravascular macrophages (20) (Fig 1). All of these macrophages may derive from sequestered monocytes in the pulmonary capillaries that migrate to the respective compartments, or may multiply by mitosis in situ (9, 21). These cells act as a portion of the lungs' defense mechanism against airborne pathogens or foreign particles that infiltrate the lung airspaces. In all mammals, blood-borne pathogens or particles that infiltrate the pulmonary tissues may be attacked by interstitial macrophages. In those species with intravascular macrophages, all particles circulating in the blood can potentially be phagocytized by intravascular macrophages before entering the interstitium.

Figure 1. Mononuclear phagocytes in the lung are a dynamic system. Large numbers of monocytes pass through the pulmonary circulation and may become transiently sequestered in pulmonary capillaries. Some of these sequestered cells migrate into the interstitium or alveolar spaces, and differentiate into mature macrophages. In some species of mammals, monocytes permanently adhere to the endothelium and differentiate into mature pulmonary intravascular macrophages. Reprinted with permission from Reference 4.