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Perivascular capillaries in the lung: An important but neglected vascular bed in immune reactions?☆

https://doi.org/10.1067/mai.2002.126836Get rights and content

Abstract

In allergic and inflammatory immune reactions of the respiratory tract, leukocytes migrate into the different compartments of the lung. The air space can easily be sampled by means of bronchoalveolar lavage. However, the subset composition in the bronchial wall or the lung interstitium often differs considerably from that of the bronchoalveolar lavage fluid. A further compartment involved in very heterogeneous immune reactions in the lung has thus far not been mentioned: the periarterial space. In numerous experiments in different species with virus, bacteria, fungi, or allergens, there was not only a leukocyte infiltration of the bronchial lamina propria but also infiltration around branches of the pulmonary artery. This thus far neglected compartment consists of a different type of capillary. Thus it is important not to overlook this area in studies on allergic or inflammatory immune reactions of the lung. (J Allergy Clin Immunol 2002;110:209-14.)

Section snippets

A unique capillary bed surrounding pulmonary arteries

Almost 20 years ago, Guntheroth and Luchtel12 examined latex casts of rat lungs using scanning electron microscopy. The airways were filled with glutaraldehyde, with a resulting transmural pressure of 10 cm H2O. The results were striking. In addition to the alveolar area with intersecting tubules, there was a different type, a thin subpleural layer, and even more relevant for this topic, long tubules of a relatively thin network of capillaries were found around pulmonary arteries (Fig 1).

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Perivascular leukocyte infiltration in different models of lung inflammation

Despite an enormous variation in the microbial and other causative agents used to induce inflammatory or asthma-like reactions, a rather constant finding is perivascular leukocyte infiltrations in the lung (Fig 3).

. Histology of branches of the pulmonary artery (PA) and bronchus (Br) . a, A pig lung after 30 minutes of normothermic isolated perfusion documenting edema formation (arrow) at this early time point (Giemsa staining; Pabst R and Binns R, unpublished data). b, An example of

Differential accumulation in the pribronchial and perivascular space

In most of the above-mentioned experiments, the authors focused on the peribronchial inflammation and mentioned the perivascular accumulations only in passing or in the legends to figures. In a few studies a more differential evaluation had been performed. Transgenic expression of GM-CSF and repeated aerosolized OVA exposure resulted not only in eosinophilic but also lymphocytic (CD4 and CD8) infiltration preferentially around pulmonary arteries.41 In mice sequentially infected with influenza

How do the leukocytes reach this perivascular area?

On the one hand, it seems to be very unlikely that leukocytes would transverse the multilayered arterial wall, including the smooth muscles, and on the other hand, it has been shown, by using electron microscopic techniques, that leukocytes can use this route,43 although this seems to be a very rare event. By using confocal laser microscopy on isolated perfused rat lungs, an upregulation of the intercellular adhesion molecule 1 in lung capillaries was documented without changes in arteriolar

Early edema formation in the perivascular space

A different aspect underlines the clinical relevance of the perivascular space of the lung in different species. In very diverse pathologic states, such as high-altitude pulmonary edema, hypervolemia, and alloxan toxicity in dogs, fluid accumulated in the perivascular space earlier than in the alveolar septa.48 In highly controlled perfusion systems of the lungs of mice49 or rats after endotoxin exposure,50 perivascular edema was frequently seen around large and medium arteries and veins.

Conclusion

The space around the branches of pulmonary arteries in the lung has been largely neglected, despite the early occurrence of edema formation and the accumulation of leukocytes in a wide variety of inflammation and allergy models in different species, which has thus far been mentioned only in passing. The perivascular capillary bed is proposed as a unique compartment, with specialized capillaries enabling a rapid exit of leukocytes (Fig 4).

. Schematic drawing of the compartments of the lung and

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    ☆

    Reprint requests: Reinhard Pabst, MD, Center of Anatomy 4120, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

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