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A Paneth cell surrogate?
  1. C A Rubio
  1. Gastrointestinal and Liver Pathology, Research Laboratory, Karolinska Institute and Hospital, 171 76 Stockholm, Sweden;Carlos.Rubio{at}onkpat.ki.se

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We read with interest the article by Cunliffe et al (Gut 2001;48:176–85) on defensin 5 stored in normal Paneth cells and in metaplastic Paneth cells in inflammatory bowel disease (IBD).

In recent years a great deal of interest has centred around Paneth cells as carriers of innate host defence, effective through their content of antimicrobial peptides and proteins.1 In humans, that mechanism seems to be conveyed by a complex system of proteins present in the granules of the Paneth cells: lysozyme, secretory phospholipase A, and probably α defensins (that is, cyptidins, so far recorded in mice).

The lysozyme rich granules in Paneth cells appears to be one of the main sources of antimicrobial peptide in the normal small bowel (where Paneth cells are normally present). Although such cells are not found in the normal colorectal mucosa, Paneth cell metaplasia may be present in the colorectal mucosa of some (but not all) patients with longstanding IBD. Demonstration of human neutrophil defensins (HNP 1–3) and lysozyme in epithelial cells of active IBD2 has fuelled interest in the molecular events behind defensin mediated intestinal host defence.

Against that background, it may be of interest to point out that another source of cytoplasmic lysozyme has recently been unveiled.3 Thirty five years ago, Azzopardi and Evans4 found mucin containing macrophages (denominated muciphages) in the colonic mucosa. Those cells were described as normal phagocytes in an otherwise normal mucosa. The mucoprotein present in their cytoplasm stained with a variety of mucus colorants (alcian blue, aldehyde fuchsin, and mucicarmine). Muciphages which were subsequently found to be associated with mucosal abnormalities induced by an inflammatory disruption of the crypts would officiate as scavengers to keep the lamina propria free from the liberated mucus. Until now, muciphages have been considered as a non-specific manifestation of mucosal damage.5

While investigating the occurrence of those cells in rectal biopsies from patients with a variety of diseases, we found muciphages either scattered in the lamina propria mucosa or distributed in a more “organised” fashion underneath the superficial epithelium and along the base of the crypts, near the muscularis mucosae.

Immunostain (CD68) confirmed the macrophagic nature of those cells and histochemistry showed the presence of PAS positive mucopolysaccharides. In addition, the cytoplasm of muciphages was strongly positive for lysozyme (Lysozyme-Muramidase stain; Dako A/S, Denmark) (fig 1).

At this stage it should be stressed that the mucus contained in the goblet cells of the crypts, in the mucus of mucous producing adenocarcinomas of the rectum, and in the mucus from a ruptured colon diverticulitis were lysozyme negative. Thus the cytoplasm of muciphages contains not only mucins but also the antimicrobial peptide lysozyme.

The presence of lysozyme in muciphages suggests that those particular macrophages are not an accidental happening but expression of a more targeted active biological mechanism of lysozyme dependent mucosal defence.

In some patients with IBD in remission, the topographical disposition of those lysozyme containing cells—between the mucosa and the underlying host (fig 1)—is noteworthy. That arrangement insinuates the possibility of an organised biological hinder (a “defensive barrier”?) against a factor(s) entering the host through the rectal mucosa.

The fact that muciphages also contain lysozyme may open new vistas for those previously unattended cells. It is conceivable that muciphages may be an important source of antimicrobial peptides in mucosae in protracted remission from earlier inflammatory episodes.

Figure 1

Rectal mucosa in remission in a patient treated in the past for ulcerative colitis. Note the arrangement of lysozyme laden muciphages along the muscularis mucosae, both underneath the superficial epithelium and at the base of the crypts (Lysozyme-Muramidase without counterstain, 25×).

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