Eva S. Leake

Comparative Cytology of Alveolar and Peritoneal Macrophages from Germfree Rats

Differences between alveolar macrophages (AM) and peritoneal macrophages (PM) have been reported by several investigators. Myrvik et al. [1], Dannenberg et al. [2], Cohn and Wiener [3], and Leake et al. [4], foundthat rabbit AM contained higher levels of hydrolases than oil-induced PM, and that AM exhibited a higher rate of endogenous oxygen consumption than oil-induced PM [4]. Oren et al. [5] studied the phagocytic process in guinea pig AM and casein-induced PM and reported that AM depend to a considerable degree upon oxidative phosphorylation as a source of energy for phagocytosis. In contrast, PM apparently depend only on glycolysis as the source of energy for that function.

In vitro effect of purified proteases of Pseudomonas aeruginosa on rabbit lung macrophages.

Abstract Purified proteases from Pseudomonas aeruginosa cause agglutination and vacuolization of rabbit alveolar macrophages after 60 min of incubation. Macrophages that had adhered to glass coverslips, when incubated in the presence of the active enzymes showed thread-like material extending in all directions and joining adjacent as well as distant cells. These changes observed on alveolar macrophages did not occur in the presence of heated proteases which were enzymatically inactive.

Interaction of Mycobacteria with Normal and Immunologically Activated Alveolar Macrophages

It is well-established that the Mycobacteria differ in their virulence for various laboratory animals. The mechanisms by which Mycobacteria express virulence could be the result of a combination of several factors including a) some form of toxic factor elaborated by Mycobacteria, b) destruction of the phagosomal membrane allowing Mycobacteria to escape and grow in the cytoplasm of macrophages, c) inhibition of lysosome fusion and d) a deficient antimicrobial system in macrophages even in the face of normal lysosome-phagosome fusion, especially in non-immunologically activated macrophages.

Mechanisms of Toxicity of Tubercle Bacilli for Macrophages

The early studies of Lurie1 clearly established that virulent tubercle bacilli are highly infectious for susceptible hosts. For example, he observed repeatedly that one colony-forming unit (CFU) of the highly virulent H37Rv strain of Mycobacterium tuberculosis could develop one tubercle in the lungs of susceptible rabbits. Although not proved at that time, it is likely that even one organism is capable of producing one tubercle in the lungs of NZW rabbits (noninbred). By contrast, the H37Ra strain, an avirulent mutant of the H37Rv strain, is incapable of replicating in the macrophages of normal rabbits. Lurie’s findings were particularly important with respect to the multiplication of the attenuated BCG strain of Mycobacterium bovis. In this case, even though BCG could not produce progressive infection in the rabbit, it was able to multiply in normal alveolar macrophages (AM) essentially at the same rate as the virulent H37Rv strain prior to the time specific cell-mediated immunity was acquired. All these early studies indicated that normal AM are incapable of inhibiting or containing the multiplication of phagocytosed organisms of the virulent H37Rv strain of M. tuberculosis, as well as the attenuated BCG strain during the early intervals after infection. Accordingly, Lurie concluded that all the immunity expressed against M. tuberculosis is acquired after infection. Lurie also demonstrated that macrophages from immune animals were resistant to the replication of virulent mycobacteria. These observations suggested that pathogenic mycobacteria have some virulence mechanism that enables them to multiply in normal macrophages, whereas immunologically activated macrophages are capable of inhibiting the growth of virulent mycobacteria.