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Background: Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function.

Pulmonary intravascular macrophages (PIMs) are constitutively found in species such as cattle, horse, pig, sheep, goat, cats, and whales and can be induced in species such as rats, which normally lack them. It is believed that human lung lacks PIMs, but there are previous suggestions of their induction in patients suffering from liver dysfunction. Recent data show induction of PIMs in bile-duct ligated rats and humans suffering from hepato-pulmonary syndrome. Because constitutive and induced PIMs are pro-inflammatory in response to endotoxins and bacteria, there is a need to study their biology in inflammatory lung diseases such as sepsis, asthma, chronic obstructive pulmonary diseases, or hepato-pulmonary syndrome. We provide a review of PIM biology to make an argument for increased emphasis and better focus on the study of human PIMs to better understand their potential role in the pathophysiology and mechanisms of pulmonary diseases.constitutive pulmonary intravascular macrophages; induced pulmonary intravascular macrophages; human lung ONE OF THE STATEMENTS FROM a workshop on pulmonary immunobiology and inflammation sponsored by the National Heart, Lung, and Blood Institute in 1999 was, "In humans, the relative roles of endothelium, pulmonary intravascular macrophages, neutrophils, or other pulmonary cells in the clearance and processing of microorganisms and antigens from the systemic venous blood are poorly defined" (15). Since then, there has been significant advancement in understanding the roles of many of the indicated cells. However, the progress has been limited for the pulmonary intravascular macrophages (PIMs). We provide a focused review of the biology of PIMs to underscore a need to study their role in human lung disease.The role of vascular inflammation in regulating the organ and systemic inflammatory responses is well established. In this context, the contributions of intravascular mononuclear phagocytes such as hepatic Kupffer cells in microbial inflammation are well understood. In contrast, the PIMs are much lesser known and appreciated for their potential influence on lung physiology. PIMs range from 20 to 80 m in diameter and typically are firmly attached to the capillary endothelium on the thicker side of the alveolar septum, presumably to minimize the impact on gas exchange, in species such as cattle, horse, sheep, goat, and pigs (56, 64). PIMs' identity as macrophages in species such as cattle and horse was confirmed in situ through phenotyping with anti-macrophage antibodies (36,49). Although sheep lung is credited with the highest concentration of PIMs, which cover 20% of the capillary endothelium (56), the horse PIMs are the largest in size. The plasma membrane of PIMs exhibits a uniquely enhanced glycocalyx through decoration with lipid or lipoprotein globules of 50 -200 nm in size (Fig.

The expression of the alpha(v)beta(3)-integrin in nonproliferating vascular beds remains unclear. To determine possible organ-specific differences, we compared alpha(v)beta(3)-integrin expression in the lung and other organs. Paraffin-embedded tissue sections of lung, liver, brain, muscle and skin obtained from rats were processed for immunohistochemistry with a monoclonal (LM609) and a polyclonal antibody (AB1903) against the alpha(v)beta(3)-integrin. Immunogold electron microscopy was used to localize alpha(v)beta(3)-integrin in rat lung microvasculature. With the use of custom-designed primers, lung sections were subjected to in situ PCR in a thermal cycler to amplify alpha(v) or beta(3) mRNA. To confirm specific amplification, PCR products were further hybridized in situ with an alpha(v) or beta(3) cDNA probe. In the lung, the alpha(v)beta(3)-integrin protein as well as alpha(v) and beta(3) mRNAs was extensively evident in the endothelium of extra-alveolar and alveolar microvessels, in vascular smooth muscle, and in large bronchial epithelium but not in the epithelium of alveolar ducts or alveoli. Ultrastructural immunogold labeling showed the presence of the integrin on the luminal and abluminal faces of the lung microvascular endothelium but not on the apical surface of the alveolar epithelium. Staining for the integrin was generally negative in blood vessels of several systemic organs, although weak staining was evident in branches of the hepatic portal vein. The constitutive presence of the alpha(v) and beta(3) mRNAs and the alpha(v)beta(3)-integrin in the lung microvascular bed suggests that gene transcription for the integrin is ongoing in lung vessels. Because it binds vitronectin, the lung vascular alpha(v)beta(3)-integrin may play a role in ligation of bloodborne, vitronectin-containing macromolecular complexes formed in inflammation.