Reference: Bio/. Bull 178: 21-24. (February. 1990) Putative Immunological Influence Upon Amphibian Forelimb Regeneration. II. Effects of X-Irradiation on Regeneration and Allograft Rejection RAYMOND E. SICARD AND MARY F. LOMBARD Department of Pediatrics, Rhode Island Hospital. Providence, Rhode Island 02903, and Department of Biology. Regis College, Weston, Massachusetts 02193 Abstract. Influence of the immune system on epimor-phic regeneration of amphibian limbs has been suggested but not proved. The present investigation explored this hypothesis by examining the effects of x-irradiation on forelimb regeneration and rejection of skin allografts. Two kRad x-irradiation was provided either to a single limb or as whole-body irradiation to intact newts (with 1 limb shielded). Complete suppression of regeneration was observed when limbs to be amputated were irradi-ated directly. In addition, irradiated limbs displayed se-vere and protracted inflammation, with total resorption of the affected limbs in 85% of the cases. Moreover, delays in both the rate of forelimb regeneration and allograft rejection were found in animals receiving whole-body irradiation. However, in these cases neither forelimb regeneration nor allograft rejection were sup-pressed. These observations diffuse the challenge raised by irradiation studies to the notion of possible immuno-logical influence on epimorphic regeneration. Moreover, the delays observed in both regeneration rate and allo-graft rejection following whole-body irradiation are con-sistent with possible interaction between the immune system and the regenerating limb. Nevertheless, confir-mation that such interaction occurs and is integral to epi-morphic regeneration must await further investigations. Introduction Epimorphic regeneration of lost appendages in verte-brates is accomplished by a mass of dedifferentiated tis-sues the regeneration blastema. This mass of tissue is derived at the site of amputation (Butler, 1935: Brunst Received 30 December 1988: accepted 30 November 1989. and Cheremetieva, 1936; Butler and O'Brien, 1942). Al-though it has been well-established that the blastema is not produced by an accumulation of blood cells, an in-fluence of the immune system on the progress of regener-ation has been suggested (Prehn, 1970). This hypothesis arose because of perceived similarities between sarcomas and the regeneration blastema. In essence, this hypothe-sis considers that immunostimulation might promote blastemal growth just as mild immunostimulation pro-motes the growth of certain sarcomas (Prehn, 1970, 1972; Prehn and Lappe, 1971). The validity of this hypothesis has yet to be either con-firmed or refuted conclusively. Nevertheless, several studies have demonstrated effects on the progress of re-generation of substances that might have altered immu-nological status (Sicard, 1981; Schotte and Sicard, 1982; and Sicard and Laffbnd, 1983). These experiments em-ployed chemical interventions and assessed their impact on forelimb regeneration but not on immunological function. More recent investigations have examined pa-rameters of immunological status (Sicard and Lombard, 1989). One of these studies disclosed modified respon-siveness to T-cell mitogens during epimorphic regenera-tion (diminished responsiveness during dedifferentiation and blastema formation; augmented responsiveness dur-ing proliferative stages) but not following nonamputa-tional trauma. Another study observed reciprocal effects of graft rejection and forelimb regeneration. That is, re-generation rate could be accelerated or delayed when combined with allograft challenge, depending upon the temporal relationship between both operations. Sim-ilarly, the rate of allograft rejection could be altered by events of epimorphic regeneration. Although the results of these previous investigations 21
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